Anticancer sulfonamide hybrids that inhibit bladder cancer cells growth and migration as tubulin polymerisation inhibitors

• Main Authors: Jia Liu, Chunlai Liu, Xiling Zhang, Liu Yu, Xue Gong, Ping Wang
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: sulfonamide-dithiocarbamate; rt-112 cell; migration; tubulin polymerisation; antitumor
• Online Access: http://dx.doi.org/10.1080/14756366.2019.1639696

Novel sulfonamide-dithiocarbamate hybrids were designed and synthesised via the molecular hybridisation strategy. Among them, compound 13d displayed a potent activity with IC50 values of 0.9, 0.7, 1.9 and 2.6 µM against UM-UC-3, RT-112, RT4 and T24. Compound 13d inhibited the migration and regulated the migration-related markers (E-cadherin, N-cadherin, Vimentin, Snail and Slung) against RT-112 cells in a concentration dependent manner. By the tubulin polymerisation assay in vitro and immunostaining assay, compound 13d was identified as a novel tubulin polymerisation inhibitor. Intragastric administration of compound 13d could inhibit the growth of RT-112 cells in vivo in a xenograft mouse model with the low toxicity, indicating that it may be a leading candidate with antitumor properties to treat bladder cancer.